The hyperthyroidism of Graves' disease is thought to be caused by immunoglobulins (Ig's) which bind to the thyroid at or near TSH receptor sites and subsequently stimulate the thyroid. The ability to measure these Ig's should be useful in the diagnosis and management of Graves' disease. Most current methods to detect the abnormal Ig's of Graves' disease measure TSH binding inhibiting Ig's (TBII) or human thyroid adenylate cyclase stimulating Ig's (TSI). A newer method measures inhibition of 125I-TSH binding to TSH receptors on guinea pig fat cell membranes (fat cell binding Ig's, FBI). These methods do not necessarily measure identical Ig's. TBII are not specific for Graves' disease, being found in sera of patients with various other thyroid diseases. TBII measurement is of questionable value in predicting the course of Graves' disease after antithyroid drug withdrawal. Information on the incidence of TSI in non-Graves' thyroid diseases and the clinical usefulness of TSI measurement is limited and contradictory. The broad objectives of the proposed research are to determine the incidence and significance of TSI in various thyroid diseases, the clinical applications of TSI measurement, and the relationship between TSI, TBII and FBI. TSI will be measured by a relatively rapid and potentially clinically adaptable assay system recently developed in this laboratory. Prospective and retrospective studies will be carried out to determine 1) whether TSI measurement can predict the course of Graves' disease after antithyroid drug withdrawal, 2) whether the degree of maternal TSI positivity is of value in predicting neonatal thyrotoxicosis, 3) whether glucocorticoids or estrogen therapy is beneficial in Graves' disease and, if so, whether this effect is related to a decrease in serum TSI activity, 4) whether TSI activity, if found in non-Graves' thyroid diseases, is indicative of nonsuppressible thyroid function, and 5) whether TSI may arise secondary to thyroid injury. Finally, the incidence and significance of circulating immune complexes in thyroid disease will be studied, particularly in regard to recent suggestions that some of these complexes in sera of patients with autoimmune thyroid disease may contain TSI or TBII.